A Carbonic Anhydrase IX (CAIX)‐Anchored Rhenium(I) Photosensitizer Evokes Pyroptosis for Enhanced Anti‐Tumor Immunity

Su, Xuxian; Wang, Wenjin; Cao, Qian; Zhang, Hang; Liu, Bin; Ling, Yuyi; Zhou, Xiaotong; Mao, Zong‐Wan

doi:10.1002/ange.202115800

Cited by 23 publications

(19 citation statements)

References 49 publications

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“…Therefore, ICD induced by pyroptosis can trigger sufficient antitumor immunity, revealing potential novel therapeutic avenue to enhance the immunogenic of tumor cells. However, pyroptosis induction is currently limited to several chemotherapeutic drugs, while photosensitizers with pyroptosis initiation ability are rarely reported [ 14 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

A mitochondria-anchored supramolecular photosensitizer as a pyroptosis inducer for potent photodynamic therapy and enhanced antitumor immunity

et al. 2022

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Background The discovery of a potent photosensitizer with desirable immunogenic cell death (ICD) ability can prominently enhance antitumor immunity in photodynamic therapy (PDT). However, majority of commercially-available photosensitizers suffer from serious aggregation and fail to elicit sufficient ICD. Pyroptosis as a newly identified pattern for potent ICD generation is rarely disclosed in reported photosensitizers. In addition, the photosensitizer with excellent mitochondria-anchored ability evokes prominent mitochondria oxidative stress, and consequently induces ICD. Results Herein, a novel supramolecular photosensitizer LDH@ZnPc is reported, without complicated preparation, but reveals desirable pyroptosis-triggered ability with mitochondria anchoring feature. LDH@ZnPc is obtained through isolation of ZnPc using positive charged layered double hydroxides (LDH), and excellent mitochondria-anchored ability is achieved. More importantly, LDH@ZnPc-mediated PDT can effectively initiate gasdermin D (GSDMD)-dependent pyroptosis of tumor cells. In vitro and in vivo results verify robust ICD ability and potent tumor inhibition efficacy, and antitumor immunity towards distant tumor inhibition. Conclusions This study reveals that LDH@ZnPc can act as an excellent pyroptosis inducer with simultaneous mitochondria anchoring ability for enhancing photodynamic therapy and boosting antitumor immunity. Graphical Abstract

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Section: Introductionmentioning

confidence: 99%

A mitochondria-anchored supramolecular photosensitizer as a pyroptosis inducer for potent photodynamic therapy and enhanced antitumor immunity

et al. 2022

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“…Both GSDMD and GSDME have been focused in the field of tumor-targeted therapy, and several small molecule agents or nano-drugs targeting GSDMD and GSDME have been developed. Su et al [78] designed a carbonic anhydrase IX (CAIX)-anchored rhenium(I) photosensitizer (named CA-Re) that evokes GSDMDmediated pyroptosis to effectively stimulate tumor immunogenicity. CA-Re enhanced the maturation and antigen-presenting ability of DC and fully activated the T cell-dependent adaptive immune response in vivo.…”

Section: Activation Of Gsdm-mediated Pyroptosismentioning

confidence: 99%

The role of pyroptosis in modulating the tumor immune microenvironment

Wang

2022

Biomark Res

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The tumor immune microenvironment (TIME) plays a key role in immunosuppression in cancer, which results in tumorigenesis and tumor progression, and contributes to insensitivity to chemotherapy and immunotherapy. Understanding the mechanism of TIME formation is critical for overcoming cancer. Pyroptosis exerts a dual role in modulating the TIME. In this review, we summarize the regulatory mechanisms of pyroptosis in modulating the TIME and the potential application of targeted pyroptosis therapy in the clinic. Several treatments targeting pyroptosis have been developed; however, the majority of treatments are still in preclinical studies. Only a few agents have been used in clinic, but the outcomes are unsatisfactory. More studies are necessary to determine the role of pyroptosis in cancer, and more research is required to realize the application of treatments targeting pyroptosis in the clinic.

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“…3(a)). In addition, Su et al designed a novel photosensitizer (CA-Re) anchored to the phospholipid-based cell membrane by employing carbonic anhydrase IX (CAIX), a transmembrane protein overexpressed only on the surface of tumor cells owing to the hypoxic TME [92]. The hypoxic condition is ameliorated by CA-Re based on its ability to bind to CAIX.…”

Section: Physical Stimulus-responsive Nanoreactorsmentioning

confidence: 99%

Evoking pyroptosis with nanomaterials for cancer immunotherapy: Current boom and novel outlook

Sun

Wang

2022

Nano TransMed

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Cancer immunotherapy, including immune checkpoint blockade, has emerged as a powerful and effective clinical strategy for the treatment of tumors. However, the low response rates or systemic adverse effects owing to the heterogeneity of the tumor microenvironment limit the efficacy of cancer immunotherapy. Pyroptosis, featuring inflammation and lysis, can promote the release of large amounts of proinflammatory agents that reprogram the tumor microenvironment and is expected to achieve the transition from "cold" tumors to "hot" tumors. Therefore, understanding how to particularly evoke tumor cell pyroptosis is crucial in overcoming the adverse effects associated with the tumor microenvironment. The development of emerging nanotechnology offers an avenue for tumor-targeted drug development. Nanomaterials that can trigger tumor-specific pyroptosis have promising applications in improving the efficacy of cancer immunotherapy while reducing systemic adverse effects. Herein, we review the fundamentals of pyroptosis, and summarize the strategies of pyroptosis-based nanomaterials that have been developed recently, with emphasis on their utility and benefits in cancer immunotherapy. Furthermore, we put forth our viewpoints regarding the investigation of nanomaterials and suggest future directions for this rapidly developing field.

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A Carbonic Anhydrase IX (CAIX)‐Anchored Rhenium(I) Photosensitizer Evokes Pyroptosis for Enhanced Anti‐Tumor Immunity

Cited by 23 publications

References 49 publications

A mitochondria-anchored supramolecular photosensitizer as a pyroptosis inducer for potent photodynamic therapy and enhanced antitumor immunity

A mitochondria-anchored supramolecular photosensitizer as a pyroptosis inducer for potent photodynamic therapy and enhanced antitumor immunity

The role of pyroptosis in modulating the tumor immune microenvironment

Evoking pyroptosis with nanomaterials for cancer immunotherapy: Current boom and novel outlook

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